Anemia Drugs Increase Risk of Heart Problems, Death in Some Cases: Study

The findings of a new study indicate that people with chronic kidney disease and diabetes who respond poorly to certain anemia drugs may face an increased risk of cardiovascular problems and death from those same drugs. 

The research, which was published last week in the New England Medical Journal, focused on people who did not seem to respond well to treatments with erythropoiesis-stimulating agents such as Aranesp, Epogen and Procrit. The study’s results could provide additional guidance to doctors and the FDA on who should be kept on the highly-restricted drugs and who should be taken off them for their own safety.

Aranesp (darbepoetin alfa), Epogen (Epoetin alfa) and Procrit (Epoetin alfa) are prescribed to patients with kidney disease, anemia, HIV and cancer to stimulate bones to increase the production of red blood cells. They are also prescribed to patients preparing to undergo major non-heart surgery to reduce the number of transfusions such patients must receive. Amgen manufactures all three drugs, though Procrit is sold and marketed by Johnson and Johnson.

In 2008, Aranesp sales were $3.1 billion, and Procrit accounted for $2.46 billion in sales. Researchers estimate that by 2002, the drugs were being prescribed to nearly half of all cancer patients.

Researchers who are part of the “Trial to Reduce Cardiovascular Events with Aranesp Therapy” (TREAT) looked at 1,872 patients who were prescribed ESAs and were not receiving dialysis. They found that 471 of those patients had a poor response to the drugs, meaning that their hemoglobin level changed less than 2% after the first two doses. The patients who had a poor response were found to have a 31% increased risk of cardiovascular problems and a 41% increased chance of death over those patients with a better response to the drugs.

A number of prior studies have suggested that the drugs may increase the risks of heart attack, strokes, blood clots and death, causing sales to drop in recent years. In 2007, the FDA issued a public health advisory regarding the drugs, saying that side effects of the Anemia drugs could increase the risk of injury or death at high doses. The FDA required that the drugs add a “black box warning” alerting patients to the risk of blood clots, strokes, heart attacks and death. The black box warning is the strongest label warning the FDA can require of a medication.

In February, the FDA announced that it was restricting the prescription of the anemia drugs under a risk evaluation and mitigation strategy (REMS). Doctors and hospitals that wish to prescribe the drugs will now have to undergo special training to identify high risk users and negative side effects.  Cancer patients using the drugs are of special concern, because some studies indicate that ESAs can stimulate tumor growth. Amgen is required to oversee hospitals and doctors using the drugs as part of a cancer treatment program to ensure they are compliant with all aspects of the REMS.